Lymphangiogenomics

BECs and LECs entertain a morphogenetic cascade of events during the growth of blood and lymphatic vessels that is much more complex than the simplistic concept of a sprouting capillary with invading, migrating, and proliferating endothelial cells. We have established a number of specialized spheroidal cell differentiation and angiogenesis assays that allow the analysis of more complex endothelial cell function related to angiogenesis, lymphangiogenesis, and endothelial cell differentiation. We utilize a novel lymphatic EC transplantation assay which aids the Integrated Project´s efforts to identify novel genes involved in lymphangiogenesis.

Responsible for this project:

Prof. Dr. Hellmut Augustin

Department of Vascular Oncology and Metastasis (A190)

German Cancer Research Center (DKFZ)

Im Neuenheimer Feld 581, TP IV

D-69120 Heidelberg, Germany

Phone: +49(0)6221/42-1500

Fax: +49(0)6221/42-1515

E-mail: augustin(at)angiogenese.de

Homepage: www.angiolab.de

Selected recent publications:

1. Alajati A, Laib AM, Weber H, Boos AM, Bartol A, Ikenberg K, Korff T, Zentgraf W, Obodozie C, Graeser R, Christian S, Finkenzeller G, Stark GB, Heroult M, Augustin HG. Endosialin (tem1) is a marker of tumor-associated myofibroblasts and tumor vessel-associated mural cells. in press, 2008.
    

2. Christian S, Winkler R, Helfich I, Boos AM, Besemfelder E, Schadendorf D, Augustin HG. Spheroid-based engineering of a human vasculature in mice. Nat. Methods Am J Pathol. 172(2):486-94, 2008.
    

3. Martiny-Baron G, Korff T, Schaffner F, Esser N, Eggstein S, Marme D, Augustin HG. Inhibition of tumor growth and angiogenesis by soluble EphB4. Neoplasia 6:248-257, 2004.
    

4. Fiedler U, Scharpfenecker M, Koidl S, Hegen A, Grunow V, Schmidt JM, Kriz W, Thurston G, Augustin HG. The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood 103:4150- 4156, 2004.
    

5. Veikkola T, Lohela M, Ikenberg K, Makinen T, Korff T, Saaristo A, Petrova T, Jeltsch M, Augustin HG, Alitalo K. Intrinsic versus microenvironmental regulation of lymphatic endothelial cell phenotype and function. FASEB J 17:2006-2013, 2003.
    

6. Piossek C, Thierauch KH, Schneider-Mergener J, Volkmer-Engert R, Bachmann MF, Korff T, Augustin HG, Germeroth L. Potent inhibition of angiogenesis by D,L-peptides derived from vascular endothelial growth factor receptor 2. Thromb Haemost 90:501-510, 2003.
    

7. Fuller T, Korff T, Kilian A, Dandekar G, Augustin HG. Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells. J Cell Sci 116:2461-2470, 2003.
    

8. Fiedler U, Krissl T, Koidl S, Weiss C, Koblizek T, Deutsch U, Martiny-Baron G, Marme D, Augustin HG. Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats. J Biol Chem 278:1721-1727, 2003.
    

9. Korff T, Kimmina S, Martiny-Baron G, Augustin HG. Blood vessel maturation in a 3-dimensional spheroidal coculture model: direct contact with smooth muscle cells regulates endothelial cell quiescence and abrogates VEGF responsiveness. FASEB J 15:447-457, 2001.
    

10. Eberhard A, Kahlert S, Goede V, Hemmerlein B, Plate KH, Augustin HG. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res 60:1388-1393, 2000. Erratum in: Cancer Res 60:3668, 2000.
     

Reviews:

9. Augustin HG, Reiss Y. EphB receptors and ephrinB ligands: regulators of vascular assembly and homeostasis. Cell Tissue Res 314:25-31, 2003.
    

10. Augustin HG, Kmeta J, Alves F, Baumbach J, Eberhard A, Kahlert S, Dandekar G. Quantitating angiogenesis and assessing the causal relationship between angiogenesis and tumorigenesis: problems and progress. Ann Hematol 81(S2):S68, 2002.
     

11. Augustin HG. Tubes, branches, and pillars: the many ways of forming a new vasculature. Circ Res 89:645-647, 2001.